There is considerable morphological evidence that neutrophils can migrate through various types of epithelium. However, it is not known if the degree of permeability of the epithelium imposes restrictions on the rate or direction of leukocyte meigration. It is also unclear what effect emigrating neutrophils have on the epithelial permeability, occluding junction disassembly and reformation. To answer these questions an in vitro model systems has been developed to study transepithelial migration of human neutrophils. A monolayer of kidney epithelial cells of known permeability grown on a micropore filter is used to separate neutrophils placed in the upper compartment of a modified Boyden chemotactic chamber from a chemoattractant in the lower compartment. In this situation, a chemotactic gradient is established across the filter and neutrophils are stimulated to migrate through the occluding junctions of the polarized epithelial monolayer. The rate and direction of neutrophil migration is dependent on the orientation of the chemotactic gradient not the polarity of the epithelium. Neutrophils are able to traverse the epithelial monolayer without serum or connective tissue factors. However, as the transepithelial electrical resistance of the epithelium increases the epithelial permeability decreases and the number of emigrating neutrophils declines. Ten percent human serum causes a significant increase in neutrophil adherence to and migration across a high resistance epithelium. Heat inactivation of the serum (56 degrees C for 30 min) causes a loss in the serum-induced neutrophil adherence to the epithelium. The increase in neutrophil chemotaxis across the epithelium is maintained. Studies on the role of serum components on neutrophil adherence and epithelial permeability are in progress.